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BMJ Open Mar 2019To assess the methodological advantages and disadvantages of parallel and crossover designs in randomised clinical trials on methylphenidate for children and adolescents... (Meta-Analysis)
Meta-Analysis
Methodological advantages and disadvantages of parallel and crossover randomised clinical trials on methylphenidate for attention deficit hyperactivity disorder: a systematic review and meta-analyses.
OBJECTIVE
To assess the methodological advantages and disadvantages of parallel and crossover designs in randomised clinical trials on methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD).
DESIGN
Secondary analyses of a Cochrane systematic review.
SETTING AND PARTICIPANTS
We searched relevant databases up to March 2015 and included data from parallel and crossover randomised trials assessing children and adolescents up to 18 years with ADHD.
INTERVENTIONS
Methylphenidate compared with placebo or no-treatment interventions.
PRIMARY AND SECONDARY OUTCOMES
The primary outcomes were teacher-rated ADHD symptoms and serious adverse events. The secondary outcomes were non-serious adverse events.
RESULTS
We included 38 parallel trials (n=5111) and 147 crossover trials (n=7134). When comparing methylphenidate with placebo or no-treatment on ADHD symptoms, we found no differences between the end of parallel trials and the first-period from crossover trials (Χ²=1.06, df=1, p=0.30, I²=5.5%). We also found no differences when combining the end of first-period crossover trials with the end of parallel trials and comparing them to the end of last-period crossover trials (Χ²=3.25, df=1, p=0.07, I²=69.2%). We found no differences in serious and non-serious adverse events, and no risk of period and carryover effects. However, only two trials contributed data to the latter analyses.
CONCLUSIONS
Both parallel and crossover trials seem suitable for investigating methylphenidate in children and adolescents with ADHD, with comparable estimates on ADHD symptom severity and adverse events. However, parallel trials might still offer ethical and statistical advantages over crossover trials.
Topics: Adolescent; Child; Female; Humans; Male; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Cross-Over Studies; Methylphenidate; Randomized Controlled Trials as Topic
PubMed: 30928951
DOI: 10.1136/bmjopen-2018-026478 -
PloS One 2017To study in more depth the relationship between type, dose, or duration of methylphenidate offered to children and adolescents with attention deficit hyperactivity... (Meta-Analysis)
Meta-Analysis Review
Gastrointestinal adverse events during methylphenidate treatment of children and adolescents with attention deficit hyperactivity disorder: A systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials.
OBJECTIVES
To study in more depth the relationship between type, dose, or duration of methylphenidate offered to children and adolescents with attention deficit hyperactivity disorder and their risks of gastrointestinal adverse events based on our Cochrane systematic review.
METHODS AND FINDINGS
We use data from our review including 185 randomised clinical trials. Randomised parallel-group trials and cross-over trials reporting gastrointestinal adverse events associated with methylphenidate were included. Data were extracted and quality assessed according to Cochrane guidelines. Data were summarised as risk ratios (RR) with 95% confidence intervals (CI) using the inverse variance method. Bias risks were assessed according to domains. Trial Sequential Analysis (TSA) was used to control random errors. Eighteen parallel group trials and 43 cross-over trials reported gastrointestinal adverse events. All trials were at high risk of bias. In parallel group trials, methylphenidate decreased appetite (RR 3.66, 95% CI 2.56 to 5.23) and weight (RR 3.89, 95% CI 1.43 to 10.59). In cross-over trials, methylphenidate increased abdominal pain (RR 1.61, 95% CI 1.27 to 2.04). We found no significant differences in the risk according to type, dose, or duration of administration. The required information size was achieved in three out of four outcomes.
CONCLUSION
Methylphenidate increases the risks of decreased appetite, weight loss, and abdominal pain in children and adolescents with attention deficit hyperactivity disorder. No differences in the risks of gastrointestinal adverse events according to type, dose, or duration of administration were found.
Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Cross-Over Studies; Dose-Response Relationship, Drug; Female; Gastrointestinal Diseases; Humans; Male; Methylphenidate; Odds Ratio; Randomized Controlled Trials as Topic
PubMed: 28617801
DOI: 10.1371/journal.pone.0178187 -
The Cochrane Database of Systematic... Jul 2015Diclofenac is a nonsteroidal anti-inflammatory drug, available as a potassium salt (immediate release) or sodium salt (enteric coated to suppress dissolution in the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Diclofenac is a nonsteroidal anti-inflammatory drug, available as a potassium salt (immediate release) or sodium salt (enteric coated to suppress dissolution in the stomach). This review updates an earlier review published in the Cochrane Database of Systematic Reviews (Issue 2, 2009) entitled 'Single dose oral diclofenac for acute postoperative pain in adults'.
OBJECTIVES
To assess the analgesic efficacy and adverse effects of a single oral dose of diclofenac for moderate to severe postoperative pain, using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Relief Database, two clinical trial registries, and the reference lists of articles. The date of the most recent search was 9 March 2015.
SELECTION CRITERIA
Randomised, double-blind, placebo-controlled clinical trials of single dose, oral diclofenac (sodium or potassium) for acute postoperative pain in adults.
DATA COLLECTION AND ANALYSIS
Two review authors independently considered studies for inclusion in the review, assessed risk of bias, and extracted data. We used the area under the pain relief versus time curve to derive the proportion of participants with at least 50% pain relief over six hours prescribed either diclofenac or placebo. We calculated the risk ratio (RR) and number needed to treat to benefit (NNT). We used information on the use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse effects.
MAIN RESULTS
This update included three new studies, providing a 26% increase in participants in comparisons between diclofenac and placebo. We included 18 studies involving 3714 participants, 1902 treated with diclofenac and 1007 with placebo. This update has also changed the focus of the review, examining the effects of formulation in more detail than previously. This is a result of increased understanding of the importance of speed of onset in determining analgesic efficacy in acute pain.The largest body of information, for diclofenac potassium 50 mg, in seven studies, produced an NNT for at least 50% of maximum pain relief compared with placebo of 2.1 (95% confidence interval (CI) 1.9 to 2.5) (high quality evidence). There was a graded improvement in efficacy as doses rose from 25 mg to 100 mg, both for participants achieving at least 50% maximum pain relief, and for remedication within 6 to 8 hours. Fast-acting formulations (dispersible products, solutions, and softgel formulations) had a similar efficacy for a 50 mg dose, with an NNT of 2.4 (2.0 to 3.0). Diclofenac sodium in a small number of studies produced a lesser effect, with an NNT of 6.6 (4.1 to 17) for the 50 mg dose.Adverse event rates were low in these single dose studies, with no difference between diclofenac and placebo (moderate quality evidence).
AUTHORS' CONCLUSIONS
Diclofenac potassium provides good pain relief at 25 mg, 50 mg, and 100 mg doses. Diclofenac sodium has limited efficacy and should probably not be used in acute pain.
Topics: Acute Pain; Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal; Chemistry, Pharmaceutical; Cyclooxygenase Inhibitors; Diclofenac; Humans; Pain, Postoperative; Randomized Controlled Trials as Topic
PubMed: 26151766
DOI: 10.1002/14651858.CD004768.pub3 -
The Cochrane Database of Systematic... Jul 2015Tension-type headache (TTH) affects about one person in five worldwide. It is divided into infrequent episodic TTH (fewer than one headache per month), frequent episodic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tension-type headache (TTH) affects about one person in five worldwide. It is divided into infrequent episodic TTH (fewer than one headache per month), frequent episodic TTH (1 to 14 headaches per month), and chronic TTH (15 headaches a month or more). Ibuprofen is one of a number of analgesics suggested for acute treatment of headaches in frequent episodic TTH.
OBJECTIVES
To assess the efficacy and safety of oral ibuprofen for treatment of acute episodic TTH in adults.
SEARCH METHODS
We searched CENTRAL (The Cochrane Library), MEDLINE, EMBASE, and our own in-house database to January 2015. We sought unpublished studies by asking personal contacts and searching on-line clinical trial registers and manufacturers' websites.
SELECTION CRITERIA
We included randomised, placebo-controlled studies (parallel-group or cross-over) using oral ibuprofen for symptomatic relief of an acute episode of TTH. Studies had to be prospective and include at least 10 participants per treatment arm.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion, and extracted data. Numbers of participants achieving each outcome were used to calculate risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or number needed to treat for an additional harmful outcome (NNH) of oral ibuprofen compared to placebo for a range of outcomes, predominantly those recommended by the International Headache Society (IHS).
MAIN RESULTS
We included 12 studies, all of which enrolled adult participants with frequent episodic TTH. Nine used the IHS diagnostic criteria, but two used the older classification of the Ad Hoc Committee, and one did not describe diagnostic criteria but excluded participants with migraines. While 3094 people with TTH participated in these studies, the numbers available for any form of analysis were lower than this; placebo was taken by 733, standard ibuprofen 200 mg by 127, standard ibuprofen 400 mg by 892, and fast-acting ibuprofen 400 mg by 230. Participants had moderate or severe pain at the start of treatment. Other participants were either in studies not reporting outcomes we could analyse, or were given one of several active comparators in single studies.For the IHS-preferred outcome of being pain free at 2 hours the NNT for ibuprofen 400 mg (all formulations) compared with placebo was 14 (95% confidence interval (CI), 8.4 to 47) in four studies, with no significant difference from placebo at 1 hour (moderate quality evidence). The NNT was 5.9 (4.2 to 9.5) for the global evaluation of 'very good' or 'excellent' in three studies (moderate quality evidence). No study reported the number of participants experiencing no worse than mild pain at 1 or 2 hours. The use of rescue medication was lower with ibuprofen 400 mg than with placebo, with the number needed to treat to prevent one event (NNTp) of 8.9 (5.6 to 21) in two studies (low quality evidence).Adverse events were not different between ibuprofen 400 mg and placebo; RR 1.1 (0.64 to 1.7) (high-quality evidence). No serious adverse events were reported.
AUTHORS' CONCLUSIONS
Ibuprofen 400 mg provides an important benefit in terms of being pain free at 2 hours for a small number of people with frequent episodic tension-type headache who have an acute headache with moderate or severe initial pain. There is no information about the lesser benefit of no worse than mild pain at 2 hours.
Topics: Acetaminophen; Administration, Oral; Adult; Analgesics, Non-Narcotic; Cyclooxygenase Inhibitors; Diclofenac; Humans; Ibuprofen; Ketoprofen; Naproxen; Numbers Needed To Treat; Pain Measurement; Piroxicam; Randomized Controlled Trials as Topic; Tension-Type Headache; Time Factors
PubMed: 26230487
DOI: 10.1002/14651858.CD011474.pub2 -
The Cochrane Database of Systematic... Apr 2018Ureteral colic is a common reason for patients to seek medical care. Alpha-blockers are commonly used to improve stone passage through so-called medical expulsive... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ureteral colic is a common reason for patients to seek medical care. Alpha-blockers are commonly used to improve stone passage through so-called medical expulsive therapy (MET), but their effectiveness remains controversial. This is an update of a 2014 Cochrane review; since that time, several large randomised controlled trials (RCTs) have been reported, making this update relevant.
OBJECTIVES
To assess effects of alpha-blockers compared with standard therapy for ureteral stones 1 cm or smaller confirmed by imaging in adult patients presenting with symptoms of ureteral stone disease.
SEARCH METHODS
On 18 November 2017, we searched CENTRAL, MEDLINE Ovid, and Embase. We also searched ClinicalTrials.gov and the WHO Portal/ICTRP to identify all published/unpublished and ongoing trials. We checked all references of included and review articles and conference proceedings for articles relevant to this review. We sent letters to investigators to request information about unpublished or incomplete studies.
SELECTION CRITERIA
We included RCTs of ureteral stone passage in adult patients that compared alpha-blockers versus standard therapy.
DATA COLLECTION AND ANALYSIS
Two review authors screened studies for inclusion and extracted data using standard methodological procedures. We performed meta-analysis using a random-effects model. Primary outcomes were stone clearance and major adverse events; secondary outcomes were stone expulsion time, number of pain episodes, use of diclofenac, hospitalisation, and surgical intervention. We assessed the quality of evidence on a per-outcome basis using the GRADE approach.
MAIN RESULTS
We included 67 studies with 10,509 participants overall. Of these, 15 studies with 5787 participants used a placebo.Stone clearance: Based on the overall analysis, treatment with an alpha-blocker may result in a large increase in stone clearance (risk ratio (RR) 1.45, 95% confidence interval (CI) 1.36 to 1.55; low-quality evidence). A subset of higher-quality, placebo-controlled trials suggest that the likely effect is probably smaller (RR 1.16, 95% CI 1.07 to 1.25; moderate-quality evidence), corresponding to 116 more (95% CI 51 more to 182 more) stone clearances per 1000 participants.Major adverse events: Based on the overall analysis, treatment with an alpha-blocker may have little effect on major adverse events (RR 1.25, 95% CI 0.80 to 1.96; low-quality evidence). A subset of higher-quality, placebo-controlled trials suggest that alpha-blockers likely increase the risk of major adverse events slightly (RR 2.09, 95% CI 1.13 to 3.86), corresponding to 29 more (95% CI 3 more to 75 more) major adverse events per 1000 participants.Patients treated with alpha-blockers may experience shorter stone expulsion times (mean difference (MD) -3.40 days, 95% CI -4.17 to -2.63; low-quality evidence), may use less diclofenac (MD -82.41, 95% CI -122.51 to -42.31; low-quality evidence), and likely require fewer hospitalisations (RR 0.51, 95% CI 0.34 to 0.77; moderate-quality evidence), corresponding to 69 fewer hospitalisations (95% CI 93 fewer to 32 fewer) per 1000 participants. Meanwhile, the need for surgical intervention appears similar (RR 0.74, 95% CI 0.53 to 1.02; low-quality evidence), corresponding to 28 fewer surgical interventions (95% CI 51 fewer to 2 more) per 1000 participants.A predefined subgroup analysis (test for subgroup differences; P = 0.002) suggests that effects of alpha-blockers may vary with stone size, with RR of 1.06 (95% CI 0.98 to 1.15; P = 0.16; I² = 62%) for stones 5 mm or smaller versus 1.45 (95% CI 1.22 to 1.72; P < 0.0001; I² = 59%) for stones larger than 5 mm. We found no evidence suggesting possible subgroup effects based on stone location or alpha-blocker type.
AUTHORS' CONCLUSIONS
For patients with ureteral stones, alpha-blockers likely increase stone clearance but probably also slightly increase the risk of major adverse events. Subgroup analyses suggest that alpha-blockers may be less effective for smaller (5 mm or smaller) than for larger stones (greater than 5 mm).
Topics: Adrenergic alpha-Antagonists; Adult; Analgesics; Diclofenac; Hospitalization; Humans; Randomized Controlled Trials as Topic; Time Factors; Ureteral Calculi
PubMed: 29620795
DOI: 10.1002/14651858.CD008509.pub3 -
Biological Psychiatry Oct 2014Psychostimulant medication, most commonly the catecholamine agonist methylphenidate, is the most effective treatment for attention-deficit/hyperactivity disorder (ADHD).... (Review)
Review
BACKGROUND
Psychostimulant medication, most commonly the catecholamine agonist methylphenidate, is the most effective treatment for attention-deficit/hyperactivity disorder (ADHD). However, relatively little is known on the mechanisms of action. Acute effects on brain function can elucidate underlying neurocognitive effects. We tested methylphenidate effects relative to placebo in functional magnetic resonance imaging (fMRI) during three disorder-relevant tasks in medication-naïve ADHD adolescents. In addition, we conducted a systematic review and meta-analysis of the fMRI findings of acute stimulant effects on ADHD brain function.
METHODS
The fMRI study compared 20 adolescents with ADHD under either placebo or methylphenidate in a randomized controlled trial while performing stop, working memory, and time discrimination tasks. The meta-analysis was conducted searching PubMed, ScienceDirect, Web of Knowledge, Google Scholar, and Scopus databases. Peak coordinates of clusters of significant effects of stimulant medication relative to placebo or off medication were extracted for each study.
RESULTS
The fMRI analysis showed that methylphenidate significantly enhanced activation in bilateral inferior frontal cortex (IFC)/insula during inhibition and time discrimination but had no effect on working memory networks. The meta-analysis, including 14 fMRI datasets and 212 children with ADHD, showed that stimulants most consistently enhanced right IFC/insula activation, which also remained for a subgroup analysis of methylphenidate effects alone. A more lenient threshold also revealed increased putamen activation.
CONCLUSIONS
Psychostimulants most consistently increase right IFC/insula activation, which are key areas of cognitive control and also the most replicated neurocognitive dysfunction in ADHD. These neurocognitive effects may underlie their positive clinical effects.
Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Brain; Central Nervous System Stimulants; Child; Deep Brain Stimulation; Female; Humans; Image Processing, Computer-Assisted; Inhibition, Psychological; Magnetic Resonance Imaging; Male; Meta-Analysis as Topic; Methylphenidate; Neuropsychological Tests; Oxygen; Randomized Controlled Trials as Topic
PubMed: 24314347
DOI: 10.1016/j.biopsych.2013.10.016 -
European Child & Adolescent Psychiatry Aug 2017This study compared the clinical efficacy and safety of attention-deficit/hyperactivity disorder (ADHD) pharmacotherapy in children and adolescents 6-17 years of age. A... (Review)
Review
This study compared the clinical efficacy and safety of attention-deficit/hyperactivity disorder (ADHD) pharmacotherapy in children and adolescents 6-17 years of age. A systematic literature review was conducted to identify randomized controlled trials (RCTs) of pharmacologic monotherapies among children and adolescents with ADHD. A Bayesian network meta-analysis was conducted to compare change in symptoms using the ADHD Rating Scale Version IV (ADHD-RS-IV), Clinical Global Impression-Improvement (CGI-I) response, all-cause discontinuation, and adverse event-related discontinuation. Thirty-six RCTs were included in the analysis. The mean (95% credible interval [CrI]) ADHD-RS-IV total score change from baseline (active minus placebo) was -14.98 (-17.14, -12.80) for lisdexamfetamine dimesylate (LDX), -9.33 (-11.63, -7.04) for methylphenidate (MPH) extended release, -8.68 (-10.63, -6.72) for guanfacine extended release (GXR), and -6.88 (-8.22, -5.49) for atomoxetine (ATX); data were unavailable for MPH immediate release. The relative risk (95% CrI) for CGI-I response (active versus placebo) was 2.56 (2.21, 2.91) for LDX, 2.13 (1.70, 2.54) for MPH extended release, 1.94 (1.59, 2.29) for GXR, 1.77 (1.31, 2.26) for ATX, and 1.62 (1.05, 2.17) for MPH immediate release. Among non-stimulant pharmacotherapies, GXR was more effective than ATX when comparing ADHD-RS-IV total score change (with a posterior probability of 93.91%) and CGI-I response (posterior probability 76.13%). This study found that LDX had greater efficacy than GXR, ATX, and MPH in the treatment of children and adolescents with ADHD. GXR had a high posterior probability of being more efficacious than ATX, although their CrIs overlapped.
Topics: Adolescent; Antihypertensive Agents; Attention Deficit Disorder with Hyperactivity; Child; Female; Guanfacine; Humans; Male
PubMed: 28258319
DOI: 10.1007/s00787-017-0962-6 -
The Cochrane Database of Systematic... Nov 2017Children with autistic spectrum disorder (ASD) frequently present with inattention, impulsivity and hyperactivity, which are the cardinal symptoms of attention deficit... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Children with autistic spectrum disorder (ASD) frequently present with inattention, impulsivity and hyperactivity, which are the cardinal symptoms of attention deficit hyperactivity disorder (ADHD). The effectiveness of methylphenidate, a commonly used ADHD treatment, is therefore of interest in these children.
OBJECTIVES
To assess the effects of methylphenidate for symptoms of ADHD (inattention, impulsivity and hyperactivity) and ASD (impairments in social interaction and communication, and repetitive, restricted or stereotypical behaviours) in children and adolescents aged 6 to 18 years with ASD.
SEARCH METHODS
In November 2016, we searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, 11 other databases and two trials registers. We also checked reference lists and contacted study authors and pharmaceutical companies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that investigated the effect of methylphenidate versus placebo on the core symptoms of ASD or ADHD-like symptoms, or both, in children aged 6 to 18 years who were diagnosed with ASD or pervasive developmental disorder. The primary outcome was clinical efficacy, defined as an improvement in ADHD-like symptoms (inattention, impulsivity and hyperactivity) and in the core symptoms of ASD (impaired social interaction, impaired communication, and stereotypical behaviours), and overall ASD. Secondary outcomes examined were: rate of adverse events; caregiver well-being; need for institutionalisation, special schooling or therapy to achieve learning outcomes; and overall quality of life.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures. We combined outcome measures that used different psychometric scales, where clinically appropriate. We used a coefficient of 0.6 to calculate standard deviations and adjust for the studies' cross-over design. We considered a standardised mean difference (SMD) of 0.52 as the minimum clinically relevant inter-treatment difference. We applied the GRADE rating for strength of evidence for each outcome.
MAIN RESULTS
The studies: we included four cross-over studies, with a total of 113 children aged 5 to 13 years, most of whom (83%) were boys. We included two studies with five-year-old children since we were unable to obtain the disaggregated data for those aged six years and above, and all other participants were in our target age range. All participants resided in the USA. The duration of treatment in the cross-over phase was one week for each dose of methylphenidate. Studies used a range of outcome scales, rated by parents, teachers or both; clinicians; or programme staff. We report parent-rated outcomes separately. Risk of bias: we considered three trials to be at high risk of bias due to selective reporting and all trials to be at unclear risk of bias for blinding of participants and assessors, due to the potential for recognising the side effects of methylphenidate. We judged all trials to be at low or unclear risk of bias for other items. Primary outcomes: the meta-analysis suggested that high-dose methylphenidate (0.43 mg/kg/dose to 0.60 mg/kg/dose) had a significant and clinically relevant benefit on hyperactivity, as rated by teachers (SMD -0.78, 95% confidence interval (CI) -1.13 to -0.43; 4 studies, 73 participants; P < 0.001; low-quality evidence) and parents (mean difference (MD) -6.61 points, 95% CI -12.19 to -1.03, rated on the hyperactivity subscale of the Aberrant Behviour Checklist, range 0 to 48; 2 studies, 71 participants; P = 0.02; low-quality evidence). Meta-analysis also showed a significant but not clinically relevant benefit on teacher-rated inattention (MD -2.72 points, 95% CI -5.37 to -0.06, rated on the inattention subscale of the Swanson, Nolan and Pelham, Fourth Version questionnaire, range 0 to 27; 2 studies, 51 participants; P = 0.04; low-quality evidence). There were inadequate data to conduct a meta-analysis on the symptom of impulsivity. There was no evidence that methylphenidate worsens the core symptoms of ASD or benefits social interaction (SMD -0.51, 95% CI -1.07 to 0.05; 3 studies, 63 participants; P = 0.07; very low-quality evidence), stereotypical behaviours (SMD -0.34, 95% CI -0.84 to 0.17; 3 studies, 69 participants; P = 0.19; low-quality evidence), or overall ASD (SMD -0.53, 95% CI -1.26 to 0.19; 2 studies, 36 participants; P = 0.15; low-quality evidence), as rated by teachers. There were inadequate data to conduct a meta-analysis on the symptom of impaired communication.
SECONDARY OUTCOMES
no data were available for the secondary outcomes of caregiver well-being; need for institutionalisation, special schooling options or therapy to achieve learning outcomes; or overall quality of life. No trials reported serious adverse events. The only adverse effect that was significantly more likely with treatment was reduced appetite as rated by parents (risk ratio 8.28, 95% CI 2.57 to 26.73; 2 studies, 74 participants; P < 0.001; very low-quality evidence). Subgroup analysis by dose did not identify any significant differences in effect on our primary outcomes between low-, medium- or high-dose ranges.
AUTHORS' CONCLUSIONS
We found that short-term use of methylphenidate might improve symptoms of hyperactivity and possibly inattention in children with ASD who are tolerant of the medication, although the low quality of evidence means that we cannot be certain of the true magnitude of any effect. There was no evidence that methylphenidate has a negative impact on the core symptoms of ASD, or that it improves social interaction, stereotypical behaviours, or overall ASD. The evidence for adverse events is of very low quality because trials were short and excluded children intolerant of methylphenidate in the test-dose phase. Future RCTs should consider extending the duration of treatment and follow-up. The minimum clinically important difference also needs to be confirmed in children with ASD using outcome scales validated for this population.
Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Central Nervous System Stimulants; Child; Child, Preschool; Cross-Over Studies; Female; Humans; Male; Methylphenidate; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 29159857
DOI: 10.1002/14651858.CD011144.pub2 -
Trends in Psychiatry and Psychotherapy 2015Attention deficit hyperactivity disorder (ADHD) is a neuropsychiatric pathology that has an important prevalence among young people and is difficult to diagnose. It is... (Review)
Review
INTRODUCTION
Attention deficit hyperactivity disorder (ADHD) is a neuropsychiatric pathology that has an important prevalence among young people and is difficult to diagnose. It is usually treated with methylphenidate, a psychostimulant with a mechanism of action similar to that of cocaine. Previous studies show that repeated use of psychostimulants during childhood or adolescence may sensitize subjects, making them more prone to later abuse of psychostimulant drugs such as cocaine and methamphetamine.
OBJECTIVE
To review experimental studies in non-human models (rodents and monkeys) treated with methylphenidate during infancy or adolescence and tested for reinforcing effects on psychostimulant drugs in adulthood.
METHOD
Systematic collection of data was performed on four databases (Web of Knowledge, PsycARTICLE, PubMed and SciELO). The initial search identified 202 articles published from 2009 to 2014, which were screened for eligibility. Seven articles met the inclusion criteria and were reviewed in this study.
RESULTS
The findings indicate that early exposure to methylphenidate has an effect on an ADHD animal model, specifically, on spontaneously hypertensive strain rats, especially those tested using the self-administration paradigm.
CONCLUSION
Future studies should prioritize the spontaneously hypertensive rat strain - an animal model of ADHD. Experimental designs comparing different behavioral paradigms and modes of administration using this strain could lead to improved understanding of the effects of exposure to methylphenidate during childhood and adolescence.
Topics: Animals; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Disease Models, Animal; Female; Methylphenidate; Pregnancy; Substance-Related Disorders
PubMed: 26630401
DOI: 10.1590/2237-6089-2014-0060 -
The Cochrane Database of Systematic... Dec 2014This is an updated version of the original Cochrane review published in Issue 3, 2012. Caffeine has been added to common analgesics such as paracetamol, ibuprofen, and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the original Cochrane review published in Issue 3, 2012. Caffeine has been added to common analgesics such as paracetamol, ibuprofen, and aspirin, in the belief that it enhances analgesic efficacy. Evidence to support this belief is limited and often based on invalid comparisons.
OBJECTIVES
To assess the relative efficacy of a single dose of an analgesic plus caffeine against the same dose of the analgesic alone, without restriction on the analgesic used or the pain condition studied. We also assessed serious adverse events.
SEARCH METHODS
We searched CENTRAL, MEDLINE, and EMBASE from inception to 28 August 2014, the Oxford Pain Relief Database, and also carried out Internet searches and contacted pharmaceutical companies known to have carried out trials that have not been published.
SELECTION CRITERIA
We included randomised, double-blind studies that compared a single dose of analgesic plus caffeine with the same dose of the analgesic alone in the treatment of acute pain.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the eligibility and quality of studies, and extracted data. Any disagreements or uncertainties were settled by discussion with a third review author. We sought any validated measure of analgesic efficacy, but particularly the number of participants experiencing at least 50% of the maximum possible pain relief over four to six hours, participants reporting a global evaluation of treatment of very good or excellent, or headache relief after two hours. We pooled comparable data to look for a statistically significant difference, and calculated numbers needed to treat to benefit (NNT) with caffeine. We also looked for any numerical superiority associated with the addition of caffeine, and information about any serious adverse events.
MAIN RESULTS
We identified no new studies with available results for this update. The earlier review included 20 studies (7238 participants) in valid comparisons, but because we used different outcomes for some headache studies, the number of participants in the analyses of the effects of caffeine is now 4262 when previously it was 5243. The studies were generally of good methodological quality, using standard designs and mostly standard scales of pain measurement, although many of those treating postoperative pain were small.Most studies used paracetamol or ibuprofen, with 100 mg to 130 mg caffeine, and the most common pain conditions studied were postoperative dental pain, postpartum pain, and headache. There was a small but statistically significant benefit with caffeine used at doses of 100 mg or more, which was not dependent on the pain condition or type of analgesic. About 5% to 10% more participants achieve a good level of pain relief (at least 50% of the maximum over four to six hours) with the addition of caffeine, giving a NNT of about 14 (high quality evidence).Most comparisons individually demonstrated numerical superiority with caffeine, but not statistical superiority. One serious adverse event was reported with caffeine, but was considered unrelated to any study medication.We know of the existence of around 25 additional studies with almost 12,500 participants for which data for analysis were not obtainable. The additional analgesic effect of caffeine remained statistically significant but clinically less important even if all the known missing data had no effect; the bulk of the unobtainable data are reported to have similar results as this review.
AUTHORS' CONCLUSIONS
The addition of caffeine (≥ 100 mg) to a standard dose of commonly used analgesics provides a small but important increase in the proportion of participants who experience a good level of pain relief.
Topics: Acetaminophen; Acute Pain; Adolescent; Adult; Aged; Analgesics; Caffeine; Chemotherapy, Adjuvant; Diclofenac; Drug Synergism; Dysmenorrhea; Female; Headache; Humans; Ibuprofen; Male; Middle Aged; Pain, Postoperative; Postpartum Period; Pregnancy; Randomized Controlled Trials as Topic; ortho-Aminobenzoates
PubMed: 25502052
DOI: 10.1002/14651858.CD009281.pub3